2,4,4,6-Tetrabromo-2,5-cyclohexadienone has wide applications in synthetic organic chemistry. It is used in preparation of linear poly(phenyleneoxides) (W. Ried et al. Angew. Chem., Int. Ed. Engl. 8, 379, 1969), direct monobromination of imidazoles and N-methylindoles (V. Calo et al. J. Chem. Soc., Perkin Trans.-1, 2567, 1972); in regioselective monobromination of aromatic amines to form 4-bromoanilines in high yields (V. Calo et al. J. Chem. Soc. C, 3652, 1971); para bromination of phenols by regioselective bromination of phenols (V. Calo et al. Chem. Ind. (Milan), 53, 467, 1971); for bromination of thiophenes (C. Slemon U.S. Pat. No. 5,371,240; CA 1995, 122, 132966); for preparation of α,μ-unsaturated bromoketones. (V. Calo at el. Tetrahedron 29, 1625, 1973); for ring expansion reaction (M. Lanz et al. Helv. Chim. Acta 80, 804, 1997); for preparation of brominated algal components via bromination of myrcene. (T. Yoshihara et al. Bull. Chem. Soc. Jpn. 51, 653, 1978); for direct brominative ring closure. (T. Kato et al. Bioorg. Chem. 4, 188, 1975); for synthesis of carbocyclic molecules (I. Ichinose et al. Chem. Lett. 61, 1979); preparation of brominated polyenes and brominated dihydroionylideneacetates (Jpn. Kokai Tokkyo Koho 78,112,852; CA 1979, 90, 87701); in stereocontrolled synthesis of disubstituted tetrahydrofurans (P. C. Ting et al. J. Am. Chem. Soc. 106, 2668, 1984); for oxidative synthesis of disulphides (T. L. Ho et al. Synthesis 872, 1974); in intramolecular cyclisation of phenolic oximes as a key step in synthesis of cis,cis-aerothionin (A. R. Forrestewr et al. Justus Liebigs Ann. Chem. 66, 1978); in synthesis of 6-bromocamphene and 9-bromolongifolene (T. Onishi et al. Jpn. Kokai Tokkyo Koho JP 60,181,037; CA 1986, 104, 110003); as reagent combination for converting alcohols to azides (A. Tanaka et al. Tetrahedron Lett. 38. 3955, 1997), silylethers to alkylbromides (A. Tanaka et al. Tetrahedron Lett. 38, 7223, 1997) and tetrahydropyranylethers to alkylbromides (A. Tanaka et al. Tetrahedron Lett. 38, 1955, 1997); in several total syntheses (B. M. Trost et al. J. Am. Chem. Soc. 105, 5075, 1983; T. Kato et al. J. Chem. Soc., Chem. Commun. 1077, 1984; F. E. Ziegler et al. J. Am. Chem. Soc. 112, 2749, 1990; K. Tatsuta et al. Bull. Chem. Soc. Jpn. 70, 427, 1997; K. Tatsuta et al. Pure Appl. Chem., 68, 1341, 1996; N. D. Pearson et al. Tetrahedron Lett., 35, 3771, 1994; G. Mehta et al. J. Chem. Soc., Chem. Commun. 1319, 1986; D. Yang et al. J. Am. Chem. Soc. 120, 5943, 1998; I. C. Gonzalez et al. J. Am. Chem. Soc. 122, 9099, 2000); for allylic bromination of μ-lactam antibiotics (Jpn. Kokai Tokkyo Koho JP 59 88,489; CA 1984, 101, 170973) and as sensitizer for photooxygenation of dioxenes. (L. Lopez et al. J. Chem. Soc., Chem. Commun. 1266, 1984, and Photochem. 32, 95, 1986).
Reference is made to M. Tsubota et al. (Bull. Chem. Soc. Jpn. 45, 1252, 1972) wherein the bromination of 2,4,6-tribromophenol was carried out by employing liquid bromine. In this process, 50 mmol (8 g) of bromine was added to 37.2 mmol (12.3 g) of 2,4,6-tribromophenol at 2-3° C. in 1:1 (v/v) methanol-acetic acid. The yellow precipitate of the desired product was obtained by adding 50 ml of 10% aqueous sodium carbonate solution to the reaction mixture. The yield of the uncrystalized product with a melting point of 136° C. was 90% (15 g, 36.5 mmol).
The drawbacks of this procedure are that it requires the handling of hazardous liquid bromine and the reaction. The process requires neutralization step to neutralize the acetic acid with sodium carbonate after the completion of the reaction. Additional steps are required to recover the methanol and the sodium acetate from the effluent for its safe discharge and to make the process more economically viable and thus the process is costly. Moreover, the reaction has to be conducted at low temperature which requires special cooling devices that affect the cost of production. Moreover, this method starts tribromophenol, an already brominated phenol as raw material. Further, the process liberates hydrobromic acid as byproduct which requires sodium carbonate to neutralize along with the acetic acid. The total bromine ended up in the reaction would be not more than 50%. Besides, the yield is only 90%.
V. Calo et al. (J. Chem. Soc. C. 3652 1971) and G. J. Fox et al. (Org. Synth. Coll. Vol. VI 181, 1988) have stated a method of bromination of 2,4,6-tribromophenol employing liquid bromine. In this process, bromine and 2,4,6-tribromophenol were reacted in equimolar ratio in sodium acetate and acetic acid mixture at room temperature. The reaction mixture was poured into crushed ice to get yellow precipitates of 2,4,4,6-tetrebromo-2,5-cyclohexadienone. The crude product was dissolved in warm chloroform and allowed to crystallize on cooling to yield 61-67% of product having a melting point in the range of 125-130° C.
The drawbacks of this procedure are that it still possesses the handling of hazardous liquid bromine and requires special equipment. Moreover, 50% of the liquid bromine ends up in the effluent in the form hydrobromic acid. The effluent is hazardous as it contains sodium acetate, acetic acid and hydrobromic acid which require additional steps such as neutralization and separation for safe discharge costing production heavily.